The origin and nature of age-associated B cells (ABCs) in mice is poorly understood. Here we show that their emergence requires MHC class II and CD40/CD40L interactions, and that they express a heterogeneous immunoglobulin repertoire comparable to nave follicular and marginal zone B cell subsets. In contrast to nave B cells, ABCs display significant somatic hypermutation in their VH and V genes, indicating prior antigen encounter. These observations suggest that ABCs are a distinct memory B cell subset that accumulates during T-cell dependent responses to diverse antigens during the life of an individual. The adaptive immune response has been linked to cardiovascular disease, suggesting that potential immune intervention strategies could reduce disease severity and prolong life. To achieve this goal, we have focused on understanding the role of B cells in atherosclerosis. We are testing the role of antibody isotype using a novel mouse model, and are characterizing the antibodies produced by mouse aortic B cells.